A large variety of skin diseases is characterized by the presence of mononuclear cell infiltrates in the dermis and to some extent in the epidermis. We have investigated frozen material of 566 lesions of benign and malignant skin diseases by immunohistological methods with a panel of 20 monoclonal antibodies; quantitative studies using computer-assisted image analysis were additionally performed in 80 specimens. In all reactive lesions, mononuclear cells were arranged in distinct compartments simulating the architecture of normal lymphatic tissue. A qualitatively uniform T cell compartment (mainly helper-inducer T lymphocytes, suppressor-cytotoxic T lymphocytes, Langerhans' cells) with slight quantitative differences was found in all inflammatory skin diseases, in peritumoral infiltrates, and also in normal skin. The B cell compartment (B lymphocytes, few T lymphocytes and monocytes) is only rarely seen (some B cell lymphomas and pseudolymphomas). The monocyte compartment (monocytes, few T lymphocytes) associated with a T cell compartment is typical for granulomatous skin lesions. The epidermis forms a separate functional region, which might evolve into a lymphoepithelial compartment in diseased skin. Low-grade malignant lymphomas of the skin display similar architectural patterns as reactive lesions, whereas high-grade malignant lymphomas do not. Obviously the mononuclear cells in the skin are usually arranged in compartments and form a limited number of distinct patterns. As similar patterns are found in diseases that are completely different with respect to clinical appearance, histological features, cause, and outcome, the patterns are not disease specific but reflect general anatomical-functional relationships of inflammatory cells and the skin.